Pharmacokinetics of Drug Entry into Cochlear Fluids

The inner ear is exposed to aminoglycosides or other drugs either intentionally or as a side effect of clinical treatments directed at other regions of the body. An understanding of the effects of drugs on the inner ear requires knowledge of the pharmacokinetics of the drug once it reaches the cochlear fluids, specifically how much of it reaches different parts of the ear and how long it stays there before disappearing. Accumulating data show that drug distribution in the inner ear is complex, especially for drugs applied locally to the ear's round window membrane. Locally applied drugs do not disperse rapidly, but instead spread very slowly through the fluid spaces by diffusion so that substantial differences in drug concentration occur in different regions of the ear. In some cases, the drug may leak from the inner ear to the blood as fast as it diffuses, meaning it may never become uniformly distributed even when applied for a long period. In recent years, experimental pharmacokinetic studies have become increasingly quantitative, permitting the results to be interpreted with computer models. Simulations of the drug distribution in animals have been used as a basis to predict the likely drug distribution in the larger, human inner ear. Such studies allow clinical drug delivery protocols to be optimized to minimize inadvertent hearing loss and to deliver therapeutic levels of the drug more effectively.